tbuckley/cabot-search huggingface dataset:
Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial
Authors: Siri Lillegraven, Nina Paulshus Sundlisæter, Anna-Birgitte Aga, Joseph Sexton, Inge Christoffer Olsen, Åse Stavland Lexberg, Tor Magne Madland, Hallvard Fremstad, Christian A. Høili, Gunnstein Bakland, Cristina Spada, Hilde Haukeland, Inger Myrnes Hansen, Ellen Moholt, Till Uhlig, Daniel H Solomon, Désirée van der Heijde, Tore K Kvien, Espen A Haavardsholm
Journal: Annals of the Rheumatic Diseases (2023)

Objectives Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of tapering TNFi to withdrawal compared with stable treatment on the risk of disease activity flares in patients with RA in remission ≥1 year. Methods This randomised, open-label, non-inferiority trial was undertaken at nine Norwegian rheumatology departments. Patients with RA in remission ≥12 months on stable TNFi therapy were allocated by computer-based block-randomisation to tapering to discontinuation of TNFi or stable TNFi. Conventional synthetic disease-modifying antirheumatic co-medication was unchanged. The primary endpoint was disease flare during the 12-month study period (non-inferiority margin 20%), assessed in the per-protocol population. Results Between June 2013 and January 2019, 99 patients were enrolled and 92 received the allocated treatment strategy. Eighty-four patients were included in the per-protocol population. In the tapering TNFi group, 27/43 (63%) experienced a flare during 12 months, compared with 2/41 (5%) in the stable TNFi group; risk difference (95% CI) 58% (42% to 74%). The tapering strategy was not non-inferior to continued stable treatment. The number of total/serious adverse events was 49/3 in the tapering group, 57/2 in the stable group. Conclusion In patients with RA in remission for more than 1 year while using TNFi, an increase in flare rate was reported in those who tapered TNFi to discontinuation. However, most regained remission after reinstatement of full-dose treatment. Trial registration numbers EudraCT: 2012-005275-14 and clinicaltrials.gov: NCT01881308 .
Comprehensive isotopomer analysis of glutamate and aspartate in small tissue samples
Authors: Feng Cai, Divya Bezwada, Ling Cai, Rohit Mahar, Zheng Wu, Mario C. Chang, Panayotis Pachnis, Chendong Yang, Sherwin Kelekar, Wen Gu, Bailey Brooks, Bookyung Ko, Hieu S. Vu, Thomas P. Mathews, Lauren G. Zacharias, Misty Martin-Sandoval, Duyen Do, K. Celeste Oaxaca, Eunsook S. Jin, Vitaly Margulis, Craig R. Malloy, Matthew E. Merritt, Ralph J. DeBerardinis
Journal: Cell Metabolism (2023)

Stable isotopes are powerful tools to assess metabolism.
Longitudinal dynamics of the gut microbiome and metabolome in peanut allergy development
Authors: Yoojin Chun, Alexander Grishin, Rebecca Rose, William Zhao, Zoe Arditi, Lingdi Zhang, Robert A. Wood, A. Wesley Burks, Stacie M. Jones, Donald Y.M. Leung, Drew R. Jones, Hugh A. Sampson, Scott H. Sicherer, Supinda Bunyavanich
Journal: Journal of Allergy and Clinical Immunology (2023)
Molecular logic of synaptic diversity between Drosophila tonic and phasic motoneurons
Authors: Suresh K. Jetti, Andrés B. Crane, Yulia Akbergenova, Nicole A. Aponte-Santiago, Karen L. Cunningham, Charles A. Whittaker, J. Troy Littleton
Journal: Neuron (2023)

Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features are poorly understood. To identify molecular pathways that contribute to synaptic diversity, single-neuron Patch-seq RNA profiling was performed on Drosophila tonic and phasic glutamatergic motoneurons. Tonic motoneurons form weaker facilitating synapses onto single muscles, while phasic motoneurons form stronger depressing synapses onto multiple muscles. Super-resolution microscopy and in vivo imaging demonstrated that synaptic active zones in phasic motoneurons are more compact and display enhanced Ca2+ influx compared with their tonic counterparts. Genetic analysis identified unique synaptic properties that mapped onto gene expression differences for several cellular pathways, including distinct signaling ligands, post-translational modifications, and intracellular Ca2+ buffers. These findings provide insights into how unique transcriptomes drive functional and morphological differences between neuronal subtypes.
P769: ASTRAGALUS POLYSACCHARIDE REGULATES ANGIOGENESIS IN PATIENTS WITH APLASTIC DISORDERS BY INTERFERING WITH IL17A EXPRESSION
Authors: Mengting Xia, Xing Cui
Journal: HemaSphere (2023)

Topic: 11. Bone marrow failure syndromes incl. PNH - Biology & Translational Research Background: Aplastic anemia (AA) is a potentially life-threatening hematopoietic failure syndrome in bone marrow, characterized by low proliferation of hematopoietic cells in bone marrow (BM), peripheral blood (PB) allogeneic cell reduction and immune dysfunction. In the clinical treatment of AA, it is urgent to add new methods that can effectively improve the survival rate and quality of life of patients Aims: The aim of this paper is to verify the therapeutic effect and mechanism of Astragalus polysaccharide (APS) on aplastic anemia (AA) through network pharmacological analysis, molecular docking model combined with animal experiments, and to expand new ideas for the treatment of AA Methods: The PUBCHEM website, SwissTragetPrediction database, and Batman-TCM database were used to search and screen the processing to obtain APS targets, and the potential targets of AA were analyzed and screened in the GSE3807 dataset. Then, the intersection targets of APS and AA were obtained through the Venny website. The analysis results from the String website were imported into Cytoscope software to construct the PPI network. The two screened AA key targets were molecularly docked with APS. Finally, animal experiments were performed, and C57BL/6 mice were randomly divided into model, treatment and control groups for experiments, and survival time was recorded. Orbital blood was collected to test blood routine, and BM tissues were taken for BM biopsy, BMNC count, and immunohistochemistry to analyze the therapeutic effect of APS on AA mice. Results: 1.After searching and screening, we obtained 16579 APS targets(Fig.a), 613 AA expression up-regulated and down-regulated targets(Fig.b), and 485 intersectional targets. The PPI network was constructed by String website and Cytoscope software.(Fig.c) 2.Two key targets, IL17A, which is up-regulated in AA expression, and VEGFA, which is down-regulated in AA expression, were identified, and molecular docking showed that APS could form a stable docking pattern with them.(Fig.d) 3.In animal experiments, it was observed that the survival of the treated group was significantly better than that of the model mice.(Fig.e) 4.Blood routine test (Fig.f), bone marrow cytology test and biopsy results (Fig.g) showed that APS did have significant therapeutic effect on AA mice. 5.IHC results showed that APS treatment inhibits the expression of IL-17A and promotes the expression of VEGFA(Fig.h). Summary/Conclusion: APS can further regulate the expression of VEGFA through IL17A to improve the angiogenesis of AA.Keywords: Aplastic anemia, Angiogenesis
P977: THE VENOUS THROMBOEMBOLISM RISK ASSESMENT MODELS IN MULTIPLE MYELOMA
Authors: Tugcan Alp Kirkizlar, Onur Kirkizlar, Ahmet Muzaffer Demir, Elif Gulsum Umit
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Multiple myeloma (MM) increases the risk of thrombosis approximately 20 times, especially in the first 6 months, due to factors related to disease, patient and treatment such as monoclonal proteins, usage of central catheter, immobility, steroids, immunomodulatory drugs (IMIDs). There are some risk assesment models that predict venous thromboembolism (VTE) and the IMPEDE and PRISM scores have recently been developed in newly diagnosed MM (NDMM) patients. Aims: We aimed to reveal the incidence of VTE and its predisposing factors and survival rates in our NDMM patients and analyze the predictive power of new risk models. Methods: We included 150 MM patients with NDMM, treated and followed-up more than 6 months between January 2013 and June 2022. Results: VTE and pulmonary embolism (PE) developed in 12 patients (8%) during the first year of treatment within 150 patients. Mean and median days of VTE were 69.9 and 60 days, respectively. In 6 patients with deep venous thrombosis developed PE. One of these patients had VTE after central venous catheterization at the 8th month. Thrombosis prophylaxis such as acetylsalicylic acid, clopidogrel, low molecular weight heparin and direct oral anticoagulants (DOACs) was applied to 17 patients due to cardiac, cerebrovascular, peripheral arterial diseases, previous VTE and IMIDs. 65 patients had thromboprophylaxis during hospitalization in the first treatment cycle. While 76% of the patients had low IMPEDE score, 61.7% of 128 patients had low PRISM score. The mortality rate was 48% and the median time of survival was 36 months. No death due to thrombosis was observed. The PRISM score was statistically significant between groups with VTE and without VTE (p 0.021). In univariate logistic regression analysis; IMPEDE intermediate risk score was found to be more predictive than the low risk score in differentiating patients non-VTE (p 0.027) while none of the variables were found to be significant in predicting VTE in multivariate analysis. Median survival was 34 months in non-VTE group and 57 months in the VTE group in the Kaplan-Meier analysis but this difference was not found statistically significant (p 0.191).Summary/Conclusion: In our study we found the VTE incidence 8% in the first year of treatment median in 60 days, similar to the literature. However we could not demonstrate the survival benefit in the non-VTE group and advantage of the IMPEDE and PRISM risk scores in predicting VTE. We think that might be related to application of thromboprophylaxis during hospitalization and in the use of IMIDs, increasing mobilization with palliation of pain in daily practice and generally increasing the use of DOACs which could be consider a protective factor in treatment or prophylaxis the non-hematological indications. Keywords: Thromboprophylaxis, Multiple myeloma, Venous thromboembolism
P1015: THE EFFECT OF THERAPY ON THE COAGULATION ACTIVITY OF MICROPARTICLES IN PATIENTS WITH PRIMARY MYELOFIBROSIS
Authors: Natalia Silina, Olesia Matvienko, Natalia Korsakova, Olga Golovina, Olga Smirnova
Journal: HemaSphere (2023)

Topic: 15. Myeloproliferative neoplasms - Biology & Translational Research Background: Primary myelofibrosis (PMF) belongs to the group of Ph-negative myeloproliferative neoplasms and is characterized by thrombotic complications. It is known that a significant contribution to the development of prothrombogenic potential in patients with PMF is made by the appearance of microparticles (MP) in the bloodstream, which appear as a result of intravascular activation of blood cells. MP expresses tissue factor (TF) and procoagulant phospholipids on their surface that can enhance prothrombogenic potential of blood plasma. Thus, unsafe and effective prevention of thromboembolic complications remains a major question in the management of these patients Aims: of this study to estimate the coagulation activity of microparticles in patients with primary myelofibrosis receiving the antiplatelet and targeted therapy. Methods: The study included 24 PMF patients receiving the antiplatelet (n=10) and targeted therapy with ruxolitinib (n=14) and 30 healthy controls. Thrombin generation was measured in platelet-free plasma with Calibrated Automated Thrombinography (CAT). Following reagents were used: «FluCa-kit», «PRP-reagent», containing rTF (1pM), «MP-reagent», containing negatively charged phospholipids (4 µM), with CTI (40 µ/ml). Endogenous thrombin potential (ETP, nM*min) was evaluated. STATISTICA 12.0 was used. The results are given as median (Me) and Q1-Q3. Mann-Whitney test was used to compare the studied groups. P<0.05 was considered statistically significant. Results: The data are shown in the table. Parameters of thrombinogram in PMF patients and healthy controls (Me; Q1-Q3) - Parameters Antiplatelet therapy(n=10) Targeted therapy(n=14) Controls(n=30) ETP, nM*min(PRP-reagent) 605.42*,**487.24-887.79 362.39**270.43-498.59 471.84384.25-564.09 ETP, nM*min(MP-reagent) 729.31**450.36-1168.22 867.69**372.36-1254.87 556.59462.25-708.00 *-p<0.05 differences between antiplatelet and targeted therapy**-p<0.4 differences between patients and controls ETP (PRP-reagent) in patients receiving the antiplatelet therapy was significantly higher than it with targeted therapy and tended to increase compared to the control group (p<0.4). ETP (MP-reagent) in all patients tended to increase compared to the control group (p<0.4) but it wasn’t any differences between both groups. Conclusion: PRP-reagent and MP-Reagent allow to estimate thrombin generation which depends on procoagulant phospholipids and TF, respectively. Thus, targeted therapy with ruxolitinib in patients with primary myelofibrosis leads to a significant decrease of thrombin generation caused by phospholipids of microparticles. Keywords: Microvesicles, Therapy, Myelofibrosis
P1148: MULTI-SITE PRE-THERAPEUTIC BIOPSIES REVEALS GENETIC HETEROGENEITY IN PATIENTS WITH NEWLY DIAGNOSED DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Ditte Stampe Hersby, Anne Ortved Gang, Lars Møller Pedersen, Torsten Holm Nielsen, Marie Fredslund Breinholt, Lone Schejbel Dupont, Ditte Dencker, Peter Henrik Noergaard, Estrid Høgdall
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Diffuse large B-cell lymphoma is a heterogeneous disease, both regarding clinical and genetic presentation, response to treatment, and outcome. To enhance personalized treatment and improve patient outcome, research has sought to stratify patients based on clinical features, the International Prognostic Index (IPI), and molecular profiling, the latter showing great diversity among patients’ mutational signatures. However, a requisite for the use of tumour genetics for prognostic and predictive stratification is that the tumour sample which is sequenced is fully representative of the patient’s cancer. Aims: To explore genetic heterogeneity. We present a prospective study of multi-site biopsy sampling in newly diagnosed patients with DLBCL prior to treatment. Methods: By next generation exome sequencing (NGS), two spatially different biopsies from 16 patients were analysed using a clinical 59 gene lymphoma panel. Results: Clinically relevant differences, between the two biopsies were found in 8/16 (50%) of the patients. In six of these 8 patients, an additional mutation emerged in one of the biopsies, including pathogenic TP53 mutation in two patients. In both cases, the patients had biopsies performed from a nodal and an extra-nodal site. The TP53 mutation were found in the extra-nodal sites. Large mutational discrepancies, between the two sites, were observed in the remaining two patients – one patient displaying completely different mutational profiles between the two sites. IgG rearrangement analysis revealed this patient to be harboring two different clones. In the remaining half of the patients, the mutational profile was identical in the two biopsies from spatially different sites Summary/Conclusion: To our knowledge, this is the first study to explore intra-patient heterogeneity in multiple pre-treatment biopsies in patients with de novo DLBCL. Our findings, of mutational discrepancies in 50% of our patients, indicate that multiple biopsies from spatially different involved sites can provide additional information about the biological heterogeneity of DLBCL. This highlights the question of whether classification and/or patient selection for trials and treatment can be made based only on a single biopsy. Future research should examine the potential clinical implications of these findings for patient stratification, treatment, and survival. Keywords: Diffuse large B cell lymphoma, TP53
P1197: BRUTON’S TYROSINE KINASE INHIBITOR ZANUBRUTINIB IN RELAPSED/REFRACTORY PRIMARY DIFFUSE LARGE B-CELL LYMPHOMA OF CENTRAL NERVOUS SYSTEM: A PHASE II TRIAL
Authors: Yali Wang, Wenbin LI, Feng Chen
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Patients with primary diffuse large B-cell lymphoma of central nervous system (PCNS-DLBCL) always have adverse prognosis. Despite the high remission rate with initial high-dose methotrexate-based therapy, more than half of the patients suffered relapsed/refractory(R/R) diseases. Efficacy of bruton’s tyrosine kinase inhibitor zanubrutinib is unclear in R/R PCNS-DLBCLs Aims: To evaluate the efficacy and safety of zanubrutinib in patients with R/R PCNS-DLBCL. Methods: In the single-arm, phase II trial, we enrolled 12 patients with R/R PCNS-DLBCL after failure of high-dose methotrexate-based therapy between April 2021 to September 2022. All of them were treated with zanubrutinib,160 mg, orally twice daily alone or in combination with systematic chemotherapy until disease progression or unacceptable toxicity. The primary end point was the overall response rate (ORR). Secondary end points included complete response rate (CRR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR) and adverse events (AEs). Results: The ORR, CRR and DCR were 83.3%(10/12,95%CI:55.2,95.3), 33.3% (4/12, 95%CI:13.8,60.9) and 100% (12/12, 95%CI:75.8,100) respectively. Median PFS has not been reached at last follow-up,7 of 12(58.3%) patients revealed a PFS for more than 9 months (range, 1 to 15+ months) at a median of 3 cycles (range,1 to 8 cycles) of zanubrutinib. All 12 patients are still alive till last follow-up. Six patients (50%) experienced grade1-2 AEs. The most commonly reported AEs were rash and cytopenia. Infection, bleeding, hypertension, atrial fibrillation/flutter were not found. Subtype analyzes showed that mutation of CD79B/MYD88L265P is not a critical factor in the treatment of PCNS-DLBCL in this study. Zanubrutinib in combination with rituximab and high-dose methotrexate resulted in higher ORR (100% vs 60%, P=0.51) and CRR (42.9% vs 20%, P=1) than either alone or in combination with other systemic therapies. Summary/Conclusion: Zanubrutinib could be a preferable choice for R/R PCNS- DLBCLs, either alone or in combination with systematic chemotherapy. Keywords: Clinical trial, Lymphoma therapy, Lymphoma, CNS lymphoma
Initial glucocorticoid bridging in rheumatoid arthritis: does it affect glucocorticoid use over time?
Authors: Lotte van Ouwerkerk, Patrick Verschueren, Maarten Boers, Paul Emery, Pascal Hendrik Pieter de Jong, Robert BM Landewé, Willem Lems, Josef S Smolen, Tom WJ Huizinga, Cornelia F Allaart, Sytske Anne Bergstra
Journal: Annals of the Rheumatic Diseases (2023)

Objectives To compare the use of glucocorticoids (GC) over time in patients with rheumatoid arthritis (RA) who were or were not treated initially with GC bridging therapy. Methods Data from the BeSt, CareRA and COBRA trials were combined in an individual patient data (IPD) meta-analysis. We compared GC use between bridgers and non-bridgers at 12, 18 and 24 months from baseline with mixed-effects regression analysis. Secondary outcomes were mean cumulative GC dose until 24 months after baseline with and without the bridging period, Disease Activity Score based on 28 joints (DAS28) over time and number of disease-modifying antirheumatic drug (DMARD) changes. Results 252/625 patients (40%) were randomised to GC bridging (bridgers). Excluding the period of bridging, later GC use was low in both groups and cumulative doses were similar. Mean DAS28 was similar between the groups, but bridgers improved more rapidly (p&lt;0.001) in the first 6 months and the bridgers required significantly fewer changes in DMARDs (incidence rate ratio 0.59 (95% CI 0.38 to 0.94)). GC use was higher in the bridgers at t=12 months (OR 3.27 (95% CI 1.06 to 10.08)) and the bridging schedules resulted in a difference in cumulative GC dose of 2406 mg (95% CI 1403 to 3408) over 24 months. Conclusion In randomised trials comparing GC bridging and no GC bridging, bridgers had a more rapid clinical improvement, fewer DMARD changes and similar late use of GC compared with non-bridgers. GC bridging per protocol resulted, as could be expected, in a higher cumulative GC dose over 2 years.
<i>Vital Signs</i>: Maternity Care Experiences — United States, April 2023
Authors: Yousra A. Mohamoud, Elizabeth Cassidy, Erika Fuchs, Lindsay S. Womack, Lisa Romero, Lauren Kipling, Reena Oza-Frank, Katharyn Baca, Romeo R. Galang, Andrea Stewart, Sarah Carrigan, Jennifer Mullen, Ashley Busacker, Brittany Behm, Lisa M. Hollier, Charlan Kroelinger, Trisha Mueller, Wanda D. Barfield, Shanna Cox
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Maternal deaths increased in the United States during 2018-2021, with documented racial disparities. Respectful maternity care is a component of quality care that includes preventing harm and mistreatment, engaging in effective communication, and providing care equitably. Improving respectful maternity care can be part of multilevel strategies to reduce pregnancy-related deaths.CDC analyzed data from the PN View Moms survey administered during April 24-30, 2023, to examine the following components of respectful care: 1) experiences of mistreatment (e.g., violations of physical privacy, ignoring requests for help, or verbal abuse), 2) discrimination (e.g., because of race, ethnicity or skin color; age; or weight), and 3) reasons for holding back from communicating questions or concerns during maternity (pregnancy or delivery) care.Among U.S. mothers with children aged <18 years, 20% reported mistreatment while receiving maternity care for their youngest child. Approximately 30% of Black, Hispanic, and multiracial respondents and approximately 30% of respondents with public insurance or no insurance reported mistreatment. Discrimination during the delivery of maternity care was reported by 29% of respondents. Approximately 40% of Black, Hispanic, and multiracial respondents reported discrimination, and approximately 45% percent of all respondents reported holding back from asking questions or discussing concerns with their provider.Approximately one in five women reported mistreatment during maternity care. Implementing quality improvement initiatives and provider training to encourage a culture of respectful maternity care, encouraging patients to ask questions and share concerns, and working with communities are strategies to improve respectful maternity care.
All Knitted and Integrated Soft Wearable of High Stretchability and Sensitivity for Continuous Monitoring of Human Joint Motion (Adv. Healthcare Mater. 21/2023)
Authors: Ujjaval Gupta, Jun Liang Lau, Pei Zhi Chia, Ying Yi Tan, Alvee Ahmed, Ngiap Chuan Tan, Gim Song Soh, Hong Yee Low
Journal: Advanced Healthcare Materials (2023)

Healthcare Wearables This image for article 2202987 by Ujjaval Gupta, Gim Song Soh, Hong Yee Low, and co-workers represents the emergence of wearable sensors, knitted with fully integrated circuitry, for biomedical or sports applications. It depicts how human movement can be captured as electrical signals by stretching the knitted conductive loops. This enables unsupervised monitoring of joints without disrupting the user's lifestyle.